The objective of the proposed work is the further investigation and characterization of the norepinephrine (NE) receptor coupled adenylate cyclase system in the limbic forebrain and in other brain structures with noradrenergic projections. Emphasis will be placed on a) The elucidation of the molecular mechanisms underlying homospecific (mediated through NE) and heterospecific (mediated by endocrine and/or neuroendocrine factors and by drugs which do not modify the availability of the specific agonist NE) regulation of the sensitivity of the NE receptor coupled adenylate cyclase system. b) The elucidation of the physiological role of NE receptors which are not beta in nature. c) The investigation of the neurobiological consequences of the pharmacologically induced changes in sensitivity of the system and d) An evaluation of the implications of the pharmacological findings for a receptor pathology of affective disorders.